This proposal outlines the development of a transgenic rat model for short-term screening of suspected nutagens. The recent use of lambda phage shuttle vectors in transgenic mice makespossible the rapid in vivo screening of mutations. Such systems will permit quantitative tissue specific determination of mutant rates, and coupled with additional quantitative measures (e.g. DNA adduct levels) will allow for direct determination of the contribution of metabolic processes, cell proliferation, detoxification, DNA repair, and the route of dosing on mutagenesis. the logical extension of this system to rats will permit direct species comparison at the molecular level for chemical screening. Currently, humanrisk assessment is performed throu the extrapolation of tumorgenicity data obtained from multiple species testing (usually mouse and rat). The capability of directly monitoring mutations in two different species should improve interspecies extrapolation to humans through an increased mechanistic understanding of how chemicals differentially induce mutations.